Intranasal Delivery of BACE1 siRNA and Rapamycin by Dual Targets Modified Nanoparticles for Alzheimer's Disease Therapy

Aleuria aurantia lectin (AAL) and β-amyploid (Aβ)-binding peptides (KLVFF) modified PEGylated dendrigraft poly-L-lysines (DGLs) encapsulate small interfering RNA of β-site precursor protein (APP) cleaving enzyme-1 (BACE1 siRNA) and rapamycin for Alzheimer's disease (AD) treatment by nasal administration. Dual target modific ation increases about 1.4-fold of drug accumulation in the brain. Furthermore, the combination of BACE1 siRNA, rapamycin, and KLVFF greatly improves the cognition of transgenic AD mice. AbstractAlzheimer's disease (AD), as a progressive and irreversible brain disorder, remains the most universal neurodegenerative disease. No effective therapeutic methods are established yet due to the hindrance of the blood-brain barrier (BBB) and the complex pathological condition of AD.   Therefore, a multifunctional nanocarrier (Rapa@DAK/siRNA) for AD treatment is constructed to achieve small interfering RNA of β-site precursor protein (APP) cleaving enzyme-1 (BACE1 siRNA) and rapamycin co-delivery into the brain, based onAleuria aurantia lectin (AAL) and β-amyploid (Aβ)-binding peptides (KLVFF) modified PEGylated dendrigraft poly-l-lysines (DGLs) via intranasal administration. Nasal administration provides an effective way to deliver drugs directly into the brain through the nose-to-brain pathway. AAL, specifically binding to L-fucose located in the olfactory epithelium, endows  Rapa@DAK/siRNA with high brain entry efficiency through intranasal admin...
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research